EP1129694A1 - Use of components for modifying physico-chemical properties of the skin and/or the mucosal tissue as adhesion prevention/decreasing adhesion agents for microorganisms - Google Patents

Abstract

The present invention relates to the use, as active ingredient, in cosmetic compositions or for the preparation of pharmaceutical compositions, of an effective quantity of at least one compound free of carbohydrate units, modifying the physicochemical properties of the surface of the skin and/or of the mucous membranes, so as to prevent or reduce the adhesion of microorganisms to the skin and/or the mucous membranes, chosen so that the decimal logarithm of the mean number of viable bacteria adhering to the epidermis, after a test consisting in bringing the said epidermis into contact with the test compound for 2 hours at 37° C., is at least 0.3 less than that obtained by a test carried out with water under the same conditions.

Description

The invention relates to the use of compounds for modify the physico-chemical properties of the skin surface and / or mucous membranes in a cosmetic composition or for the preparation of a pharmaceutical composition as agents preventing or decreasing the adhesion of microorganisms, particularly bacteria, on the skin and / or mucous membranes.

Human skin is permanently populated by a multitude of different microorganisms (bacteria, yeasts and fungi). The resident microbial flora, essential for good skin health, consists mainly of staphylococci ( Staphylococcus epidermis and Staphylococcus hominis ), corynebacteria, Gram + propionibacteria such as Propionibacterium acnes , as well as a fungal flora mainly composed of Pytosporum ovale .

Skin infections are most often due to the disruption of the ecological balance of the resident flora following the colonization of the skin by pathogenic exogenous germs or the abnormal proliferation of an endogenous strain. The best known pathogens are Pseudomonas aeruginosa (Gram -) which is responsible for small pimples, folliculitis, redness and pruritus, Candida albicans which can cause inflammation at the commissure of the lips, cutaneous candidiasis, pruritus, folliculitis and canker sores, Staphylococcus aureus which can cause pimples, folliculitis, impetigo, and boils, and group A Streptococcus responsible for impetigo.

To combat these microorganisms, it is common to use antibiotics or bactericides. The use of these compounds poses however the problem of the non-specificity of action aimed indifferently pathogenic flora and resident flora, and the problem of risk the appearance of bacterial resistance, as well as skin tolerance (irritations, allergies, ...).

It is also known to reduce or prevent colonization surfaces such as teeth, skin and / or mucous membranes, by germs pathogens by preventing their attachment to these supports. Compounds used as anti-adhesion agents described in the prior art are carbohydrates and carbohydrate derivatives (WO 96 23 479, EP 380 084, US 5,002,759, US 4,859,656, WO 81 03 175, WO 93 14 773, WO 95 15 149, WO 95 07 084 and WO 95 17 898).

However, most carbohydrates are a source of carbon for bacteria and fungi. Their presence in compositions cosmetics therefore promotes microbial proliferation and requires increasing the concentration of preservatives (bactericides or bacteriostats). This drawback thus cancels the benefit of the approach of replacing antibiotic compounds or bactericides by compounds that reduce microbial adhesion.

The Applicant has surprisingly found that a group specific compounds, free of carbohydrate units, significantly reduced microbial adhesion to the skin and / or mucous membranes and thereby prevent the proliferation of germs potentially pathogenic in the absence of antibiotic agents, bactericides or fungicides.

These compounds, unlike carbohydrates which are bind to receptors of microorganisms to prevent binding to corneocyte glycolipids, act on the physicochemical properties of the surface of the skin and / or mucous membranes, these properties physicochemical involving electrodynamic interactions due to Van der Waals forces, the acid-base interactions according to Lewis and electrostatic interactions.

In addition, these compounds are not bactericidal. Therefore, they do not do not cause unwanted side effects on the skin and / or mucous membranes.

The compounds according to the invention, used as principles active, reduce or prevent adhesion of a microorganism whose overall surface charge is negative or positive in increasing the negative or positive charge of the skin, respectively so as to cause repulsion between the skin and / or mucous membranes and the microorganism.

The compounds according to the invention, used as principles active, further reduce or prevent the adhesion of a micro-organism, limiting Van-type interactions as much as possible der Waals between the skin and / or mucous membranes and the micro-organism, favoring repulsive acid-base interactions according to Lewis and in limiting the attractive acid-base interactions according to Lewis between the microorganism and the skin and / or mucous membranes.

By preventing or reducing the adhesion of microorganisms, it should be understood that the compound or the composition containing it may be used both preventively, for its ability to prevent, totally or partially, the adhesion of microorganisms, only as a curative for its ability to facilitate the detachment of microorganisms.

These compounds are chosen so that the logarithm decimal of the average number of viable bacteria adhering to the epidermis reconstructed, after a test for bringing said epidermis into contact with the compound tested for 2 hours at 37 ° C, which is at least 0.3 less than that obtained by a test carried out with water under the same conditions.

The reconstructed epidermis used in the test indicated above is the reconstituted human epidermis, equivalent to human skin, sold by the company EPISKIN.

This test assesses changes in properties physico-chemical surface of the skin and / or mucous membranes, making intervene the Van der Waals electrodynamic interactions, acid-base interactions according to Lewis and the interactions electrostatic.

The subject of the invention is therefore the use as a principle active, in a cosmetic composition or for the preparation of a pharmaceutical composition, of an effective amount of at least one compound free of carbohydrate units, modifying the properties physicochemical of the surface of the skin and / or mucous membranes, in view prevent or reduce the adhesion of microorganisms to the skin and / or mucous membranes, chosen so that the decimal logarithm of the average number of viable bacteria adhering to the reconstructed epidermis, after a test for bringing said epidermis into contact with the compound tested for 2 hours at 37 ° C, which is at least 0.3 less than that obtained with a test carried out with water under the same conditions.

Preferably, the compounds for which the decimal logar above defined is less than 0.5 and more particularly lower by 1 than that of water under the same conditions.

The experimental protocol for choosing these compounds will be defined below.

These compounds can be of completely different natures and can be chosen, by way of nonlimiting example, from bodies non-solid fat at room temperature, polymers, surfactants and / or their mixtures.

The compounds used according to the invention may very well be hydrophilic or lipophilic.

Use is more preferably made, as active principle in a cosmetic composition or for the preparation of a pharmaceutical composition, of an effective amount of compounds free of carbohydrate units modifying the physicochemical properties of the surface of the skin and / or mucous membranes chosen from surfactants such as disodium cocoamphodiacetate, oxyethylenated glyceryl cocoate (7 EO) such as the product sold by the company COGNIS under the name Cetiol HE, hexadecenylsuccinate 18, PPG-15 stearyl ether; "monoethanol monosulfosuccinate salts ricinole amide such as the product sold by the company Goldschmidt under the name REWODERM 51333, the hydrogenated ricinole triglyceride oxyethylenated with 60 ethylene oxide units as the product sold by the company Nikko under the name NIKK OL HCO-60 or, like the product sold by the company BASF under the name CREMOPHOR RH60 ", polymers such as Poloxamers, which are block copolymers of ethylene oxide and propylene oxide, such as for example the product sold under the name Lutrol F68 by the company BASF and the Poloxamer 407 sold under the name SYNPERONIC PE / F 127 by the company UNIQEMA; "polyacrylamide / C13-14 Isoparaffin / Laureth-7 as the product sold by the company SEPPIC under the name SEPIGEL 305". Non-solid fatty substances at room temperature (that is to say at a temperature ranging from about 20 to 35 ° C) such as sesame oil, sweet almond oil, almond oil d apricot, sunflower oil, octoxyglyceryl palmitate (or ethyl-2-hexyl glyceryl ether palmitate) as the product sold under the name Mexanyl GP by the company Chimex, octoxyglyceryl behenate (or behenate d 'ethyl-2-hexyl glyceryl ether), dioctyl adipate, tartrate of di-alcohols C ₁₂ -C ₁₃ branched as the product sold under the name Cosmacol ETI by the company Enichem.

According to the invention, the compound (s) or the composition are used the container (s) applied topically to the skin and / or mucous membranes.

The adhesion of microorganisms to the skin and / or mucous membranes has consequences that range from simple annoyance (smell, small pimples, ...) to more or less serious diseases.

One of the aspects of the invention is therefore to propose the use of a compound free of carbohydrate units as a principle active in a cosmetic composition or for the preparation of a pharmaceutical composition.

In particular, the invention relates to the use cosmetic in topical application of at least one compound as active ingredient in a cosmetic composition intended to reduce bad body odors and / or intended for hygiene care bodily.

By personal hygiene care is meant all substances or preparations intended to be put in contact with the various parties surface of the human body and / or with teeth and / or mucous membranes in order to clean them, protect them, keep them in good condition, modify the appearance, perfume them or correct their odor.

In particular, the invention relates to the use cosmetic in topical application of at least one compound as active ingredient in a cosmetic composition intended to combat blackheads and / or dandruff.

The microbial flora of the skin surface is responsible of a large number of disorders.

Thus, the invention also relates to the use of at least a compound as an active ingredient for the preparation of a pharmaceutical composition intended for use in application topical to fight against fungal infections and / or acne, particularly juvenile acne.

The amount of compound usable according to the invention depends well obviously of the desired effect and must be an effective amount for partially or totally prevent adhesion of microorganisms or to facilitate the detachment of microorganisms.

By way of example, the amount of compound usable according to the invention can range, for example, from 0.1 to 100%, preferably from 0.5 to 50% and more particularly from 1 to 25% of the total weight of the composition.

The invention also relates to a cosmetic process for treat disorders associated with the adhesion of microorganisms consisting of applying to the skin a cosmetic composition comprising at least a compound according to the invention in a cosmetically acceptable medium.

By cosmetically acceptable medium is meant a medium compatible with the skin, scalp, mucous membranes, nails, and hair .

The cosmetic and pharmaceutical compositions used according to the invention can be presented in all dosage forms normally used for topical application, especially under form of an aqueous, hydroalcoholic or oily solution, a oil-in-water or water-in-oil or multiple emulsion of an aqueous gel or oily, a liquid, pasty or solid anhydrous product or a dispersion of oil in an aqueous phase using spherules, these spherules which may be polymeric nanoparticles such as nanospheres and nanocapsules, or better, lipid vesicles of ionic and / or non-ionic type.

When the composition according to the invention comprises a phase fatty, this represents, preferably, from 1 to 60% of the total weight of the composition.

• les silicones volatiles ou non-volatiles, linéaires, ramifiées ou cycliques, organo-modifiées ou non, hydrosolubles ou liposolubles,
• les huiles minérales telles que l'huile de paraffine et de vaseline,
• les huiles d'origine animale telles que le perhydrosqualène,
• les huiles d'origine végétale telles que l'huile d'amandes douces, l'huile d'avocat, l'huile de ricin, l'huile d'olive, l'huile de jojoba, l'huile de sésame, l'huile d'arachide, l'huile de macadamia, l'huile de pépins de raisin, l'huile de colza, l'huile de coprah,
• les huiles synthétiques telles que les isoparaffines,
• les huiles fluorées et perfluorées,
• les esters d'acides gras.

This fatty phase can comprise one or more oils preferably chosen from the group consisting of:

• volatile or non-volatile, linear, branched or cyclic, organo-modified or not, water-soluble or liposoluble silicones,
• mineral oils such as paraffin oil and petrolatum,
• oils of animal origin such as perhydrosqualene,
• oils of vegetable origin such as sweet almond oil, avocado oil, castor oil, olive oil, jojoba oil, sesame oil, peanut oil, macadamia oil, grape seed oil, rapeseed oil, coconut oil,
• synthetic oils such as isoparaffins,
• fluorinated and perfluorinated oils,
• fatty acid esters.

It can also contain as fat (a) or several fatty alcohols, fatty acids or waxes (paraffin, wax polyethylene, Carnauba, beeswax).

In a known manner, the compositions used in the invention may also contain adjuvants customary in the field cosmetics such as conventional gelling agents and / or thickeners hydrophilic or lipophilic; hydrophilic or lipophilic active agents; of preservatives; solvents; antioxidants; perfumes; of emulsifiers; moisturizers; pigmenting agents; of depigmenting; keratolytic agents; vitamins; emollients; sequestrants; surfactants; polymers; agents basifying or acidifying; charges; anti-free radical agents; ceramides; sun filters (especially ultraviolet); of insect repellents; slimming agents; coloring matters; anti-dandruff.

The quantities of these various adjuvants are those conventionally used in the fields considered.

Of course, those skilled in the art will take care to choose the optional compounds to be added to the composition according to the invention, in such a way that the advantageous properties intrinsically attached to the composition according to the invention is not, or substantially not, altered by the proposed addition.

As solvents, mention may be made of organic solvents hydrophilic, and for example lower mono-alcohols, linear or branched, having from 1 to 8 carbon atoms such as ethanol, propanol, butanol, isopropanol, isobutanol; polyethylene glycols having from 6 to 80 ethylene oxides, polyols such as propylene glycol, isoprene glycol, butylene glycol, glycerol; isosorbide mono- or dialkyls whose alkyl groups have from 1 to 5 carbon atoms such as dimethyl isosorbide; glycol ethers such as diethylene glycol mono-methyl or mono-ethyl ether and propylene glycol ethers such as dipropylene glycol methyl ether.

Organic solvents can represent from 5 to 98% by weight total of the composition.

The compositions used in the present invention can be more or less fluid and have the appearance of a white or colored cream, ointment, milk, lotion, serum, paste, foam or solid.

They can optionally be applied to the skin under aerosol form.

They can also be in solid form, and by example in the form of a stick.

They can be used as a care product, such as cleaning product for the skin or hair, as a sunscreen product, as a makeup product like foundations, reds to lips, mascaras, eyeshadows, and / or as a simple deodorant product.

Thus the subject of the invention is a cosmetic composition of care, cleaning, make-up or deodorant comprising at least one compound according to the invention.

The anti-adhesion test meets the protocol below:

Before bacterial adhesion, the reconstructed epidermis is brought into contact for 2 hours with 25 mg of the product to be tested at 37 ° C. Then added 1 ml of bacterial suspension of Staphylococcus aureus at a concentration of 10 ⁷ germs / ml in Tryptone salt. After incubation for 24 hours at 37 ° C, the bacterial suspension is emptied and five rinses are carried out with 1 ml of sterile distilled water. The epidermis detached from its support is then ground using a robot in 18 ml of Tryptone salt. This suspension is decimal diluted in Tryptone salt, then 1 ml of the dilution is seeded in 15 ml of Trypticase Soy agar and incubated for 24 hours at 37 ° C. Then there are the adherent and viable cells.

This anti-adhesion test assesses the effectiveness of single molecules or finished products.

Before the anti-adhesion test, the test of following viability:

A bacteria / product mixture to be tested, in the same ratio as in the anti-adhesion test, is brought into contact for 24 hours at 37 ° C. The test can require shaking incubation to avoid bacteria death for lack of oxygen, in particular with regard to non-fatty substances solid at room temperature. The count of germs is carried out by decimal dilution in Tryptone salt and sowing with a rake of 100 µl on Trypticase Soy Agar. Counting colonies takes place after 24 hours of incubation at 37 ° C.

The viability test carried out prior to the anti-adhesion test eliminates any bactericidal component of molecules or finished products tested and to highlight only the anti-adhesion activity.

The following examples show the results obtained for different compounds tested according to the invention and a particular embodiment of composition according to the invention.

These examples are of course given by way of illustration and have not absolutely not limiting.

Examples of compounds used according to the invention:

The results obtained, for the compounds presented here, result implementation of the above detailed protocol.

The figures presented opposite the compound correspond to the decrease in the decimal logarithm of the average number of viable Staphylococcus aureus adhering to the epidermis reconstructed after treatment with the compound under the conditions defined by the previous test compared to the decimal logarithm of the average number of Staphylococcus viable aureus adheres to the reconstructed epidermis after treatment with water under the same conditions. Disodium cocoamphodiacetate 1.34 Oxyethylenated glyceryl cocoate (7 EO) 1.41 Mono ethanol mono sulfoccinate salt ricinoleic amide (tested at 5% active ingredient) 3.84 Oxyethylenated hydrogenated ricinoleic triglyacid sold under the name NIKKOL HCO-60 by the company NIKKO (tested at 10% in active material) 0.8 Poloxamer 407: copolymer of ethylene oxide, propylene oxide and ethylene oxide (98 OE / 67 OP / 98 OE) (PM: 12000) sold under the name: SYNPERONIC PE / F 127 by the UNIQEMA company 0.81 Polyacrylamide / C13-14 Isoparaffin / Laureth-7 (tested at 1% active ingredient) 1.43 Branched C ₁₂ -C ₁₃ di-alcohol tartrate 2.31 Apricot almond oil 0.81 Dioctyl adipate 0.90

Example of composition used according to the invention:

W / O emulsion for facial care: Oxyethylenated poly methyl acetyl dimethyl methyl siloxane (ABIL EM 90 ® from GOLDSCHMIDT) 3% Ethyl-2-hexyl glyceryl ether palmitate (MEXANYL GP® from CHIMEX) 10% Tartrate of branched C ₁₂ -C ₁₃ di-alcohols (COSMACOL ETI ® from ENICHEM) 10% Oxyethylenated glyceryl cocoate (7 EO) (CETIOL HE ® from GOGNIS) 3% Ethylene oxide, propylene oxide and ethylene oxide condensate (PM: 8350) (75 EO / 30 OP / 75 EO) (LUTROL F 68 ® from BASF) 3% Water QSP 100 Antioxidant qs Perfume qs

After treatment with the above composition, under the conditions defined by the previous test, there is a decrease in the decimal logarithm of the average number of viable Staphylococcus aureus adhering to the reconstructed epidermis relative to the decimal logarithm of the average number of viable Staphylococcus aureus adherent to the reconstructed epidermis after treatment with water under the same conditions of 3.96.

Claims (13)

Use in a cosmetic composition or for the preparation of a pharmaceutical composition as an active ingredient, an effective amount of at least one compound free of hydrate units carbon, modifying the physicochemical properties of the surface of the skin and / or mucous membranes, to prevent or reduce the adhesion of microorganisms on the latter, said compound being chosen so that the decimal logarithm of the average number of viable bacteria adhering to the reconstructed epidermis, after a test for bringing said contact into contact epidermis with the compound tested for 2 hours at 37 ° C, or less at least 0.3 to that obtained by a test carried out with water in the same conditions. Use in a cosmetic composition or for the preparation of a pharmaceutical composition as active principle, of an effective amount of at least one compound according to claim 1, characterized in that the decimal logarithm of the average number of adhering viable bacteria on the reconstructed epidermis, after a test for bringing said epidermis into contact with the compound tested for 2 hours at 37 ° C., is at least 0.5 less than that obtained by a test carried out with water in the same conditions. Use in a cosmetic composition or for the preparation of a pharmaceutical composition as active ingredient, of an effective amount of at least one compound according to any one of claims 1 or 2, characterized in that the decimal logarithm of the average number of viable bacteria adhering to the reconstructed epidermis, after a test for bringing said epidermis into contact with the test compound for 2 hours at 37 ° C., is at least 1 less than that obtained by a test carried out with l under the same conditions. Use according to any one of claims 1 to 3, characterized in that the active principle is chosen from surfactants, polymers and non-solid fatty substances at room temperature. Use according to any one of claims 1 to 4, characterized in that the active principle is chosen from, disodium cocoamphodiacetate, oxyethylenated glyceryl cocoate (7 EO), monoethanol monosulfosuccinate salts ricinole amide, hydrogenated ricinole triglyceride oxyethylenated with 60 ethylene units Poloxamers, polyacrylamide / C13-14 Isopraffin / laureth.7, hexadecenylsuccinate 18, sesame oil, octoxyglyceryl palmitate, octoxyglyceryl behenate, dioctyl adipate , PPG-15 stearyl ether, apricot almond oil, branched C ₁₂ -C ₁₃ di-alcohol tartrate and mixtures thereof. Use according to any one of claims 1 to 5, characterized in that the active principle is present in an amount ranging from 0.1% to 100% of the total weight of the composition. Use according to claim 6, characterized in that the active principle is present in an amount ranging from 0.5% to 50% of the total weight of the composition. Use according to any one of claims 6 or 7, characterized in that the active principle is present in an amount ranging from 1% to 25% of the total weight of the composition. Use according to any one of Claims 1 to 8, characterized in that the composition is in the form of a lotion, an aqueous gel, a serum, an emulsion or a dispersion of vesicles lipids. Cosmetic treatment method for treating disorders linked to the adhesion of microorganisms consisting in applying to the skin and / or the mucous membranes, a cosmetic composition comprising at least a compound defined according to any one of claims 1 to 5 in a cosmetically acceptable medium. Cosmetic use in topical application of at least one compound defined according to any one of claims 1 to 5, in a cosmetic composition intended to reduce bad odors and / or intended for personal hygiene care. Cosmetic use in topical application of at least one compound defined according to any one of claims 1 to 5, in a cosmetic composition intended to combat comedones and / or dandruff. Use of at least one compound defined according to one any one of claims 1 to 5, for the preparation of a pharmaceutical composition intended for use in application topical to fight against fungal infections and / or acne.